Chitin, poly-.beta.-(1.fwdarw.4)-N-acetyl-D-glucosamine, is a cellulose-like biopolymer which is the primary constituent of the cell wall in most fungi, molds, and yeasts and the exoskeleton of crustaceans and insects. The amount of chitin relative to total dry weight of these organisms is highest in crustaceans, where it is commonly found as the tough polymer matrix of crab and shrimp shells. Crustacean shells are currently the primary source of commercial chitin.
Chitosan, poly-.beta.-(1.fwdarw.4)-2-deoxy-D-glucosamine, the deacetylated derivative of chitin, has great potential value because of its free amines, for new chemical and medical applications. Chemically, chitosan's free amines possess the ability to chelate with many metals (see Muzzarelli et al., Journal of Membrane Science 16: 295-308 (1983)) and other ions. It thus has the potential for use in a wide variety of applications such as metal recovery from industrial wastes and fibers with improved dyeability, among others.
Biologically, chitin and chitosan provide sources of glucosamine, a potentiator for antibiotics (see Austin et al., Science 212: 749-753 (1981)) and consequently a substance with wound-healing properties. Chitosan is a hemostatic, and it also promotes collagen formation, thus preventing scar formation. The chemistry of chitosan also confers upon it excellent film forming properties (see Muzzarelli et al.), and it would be expected to have great utility in the formation of membranes. Its toughness can be utilized in producing high strength fibers and bioseparation films and it therefore may have other medical applications such as sutures.
Chitosan can itself be chemically modified to provide materials with other additional useful properties. Muzzarelli et al. discloses N-alkylation of chitosan as a method of varying the plasticity and other properties of membranes, fibers and other chitosan-derived materials. This method for production of various N-alkyl chitosans, however, requires the expensive chitosan as the starting material.
Chitin's ready availability and abundance, as waste material from canning food industries, allow broad research on its capabilities and make it very attractive as starting material for the synthesis of chitosan. One drawback of the natural starting product, however, is that its properties can vary considerably depending on the source and method of preparation (see Austin et al.); this could pose great difficulty in controlling and attributing the properties of the end product.
Problems have also been encountered during the production of chitosan from chitin, normally attempted by alkaline hydrolysis of the chitin. Reports have contended that solvents doped with chlorides such as LiCl are useful in adjusting the solubility of chitin during alkaline hydrolysis. Chitin, however, lacks a good direct solvent; in fact, chitin is insoluble in conventional solvent systems. Chitin is also easily degraded in the presence of acid. Therefore acid catalyzed hydrolysis is very difficult and one has to balance the rate of hydrolysis with the rate of degradation. One alternative, then, for the production of chitosan from naturally-occurring chitin would be a process involving less harsh conditions and one affording greater solubility of the starting material.
Due to the variability of chitin sources and the difficulty of working with chitin it may be advantageous to develop synthetic molecules similar to chitin and chitosan by aminating or amidating cellulosic materials. Haskins, U.S. Pat. No. 2,136,299 and Meigs, U.S. Pat. No. 1,801,053 disclose processes for the amination of carbohydrate and cellulosic materials. However these do not involve direct amination; rather they rely upon an initial step of harsh and degradative acid treatment. Dreyfus, U.S. Pat. Nos. 2,007,950; 2,186,101; and 2,233,475 disclose processes for the production of cellulosic materials containing nonacidic nitrogen, including amino groups, but the processes are not directed to any specific derivatizations or sites of derivatization. Furthermore, the amination processes do not afford direct (i.e., one-step) amination of the cellulosic materials.
Accordingly, new methods have been sought for the synthesis of chitin and chitosan under milder reaction conditions and for synthesis from more economical, tractable and homogeneous starting materials. Additionally, methods have been sought which have the regioselectivity to ensure that the important functional groups are placed as in the naturally occurring counterparts. Finally, new methods have been sought for the synthesis of N-alkylated chitosans from starting materials considerably cheaper than the parent chitosan itself.